Rat Abdominal Skin Research Articles

Formulation and Assessment of Tolnaftate Microsponges for Topical Medication Deliverance

Objective: This study aimed to develop and evaluate the sustained delivery of Tolnaftate using topical polymeric microsponges. Materials and Methods: Tolnaftate-loaded microsponges made of ethyl cellulose were prepared via quasi-emulsion solvent diffusion. The effects of the drug-to-polymer ratio on active drug content, particle size, and entrapment efficiency were examined. The optimized formulation was incorporated into a Carbopol gel and evaluated for drug content, pH, viscosity, and in vitro drug release. The study considered internal phase volume, stirring rate, and emulsifier concentration as variables and analyzed their impact on entrapment efficiency and particle size. Results: Increasing stirring speed reduced particle size and improved entrapment efficiency, while a higher volume of dichloromethane decreased particle size. Scanning electron microscopy revealed porous and spherical microsponges. The 1.5:1 drug-to-polymer ratio yielded the highest active drug content, optimal entrapment efficiency, and smallest particle size, making it the preferred ratio for further studies. Conclusions: The drug release from the microsponge gel was more sustained compared to both the marketed product and pure drug gel. An ex vivo drug deposition study using rat abdominal skin showed satisfactory drug deposition. These polymeric microsponges show potential as a topical drug delivery system for antifungal therapy.

Rosuvastatin Flexible Chitosomes: Development, In Vitro Evaluation and Enhancement of Anticancer Efficacy Against HepG2 and MCF7 Cell Lines.

Rosuvastatin (ROS), a statin drug with promising anticancer properties has a low bioavailability of approximately 20% due to lipophilicity and first-pass metabolism. This study aimed to enhance ROS anticancer efficacy through loading into flexible chitosomes. The chitosomes were prepared starting from negatively charged liposomes through electrostatic interactions with chitosan. The conversion of zeta potential from negative to positive confirmed the successful formation of chitosomes. The chitosan coating increased the particle size and zeta potential, which ranged from 202.0 ± 1.7nm to 504.7 ± 25.0nm and from - 44.9 ± 3.0 mV to 50.1 ± 2.6 mV, respectively. Chitosan and drug concentrations had an important influence on the chitosome properties. The optimum chitosome formulation was used to prepare ROS-loaded flexible chitosomes using different concentrations of four edge activators. The type and concentration of edge activator influenced the particle size, drug entrapment efficiency, and drug release rate of the flexible chitosomes. Flexible chitosomes significantly increased drug permeation through rat abdominal skin compared to control transferosomes and drug solution. The optimal ROS flexible chitosomes containing sodium deoxycholate as an edge activator had a 2.23-fold increase in ROS cytotoxic efficacy against MCF7 cells and a 1.84-fold increase against HepG2 cells. These results underscore the potential of flexible chitosomes for enhancing ROS anticancer efficacy.

Curcumin-Loaded Organogel for The Topical Skin Disorder Based on 12 Hydroxystearic Acid

Curcumin (CUR) possesses various pharmacological properties, including antibacterial and improving injury healing. This work aimed to formulate curcumin organogel using 12 hydroxy stearic acid as gelator with tween 80 as surfactant and PEG 400 as co surfactant to improve the CUR permeation through the skin. The CUR organogels were prepared using different 12HSA concentrations with solvents sesame oil (SO), and orange oil (OO), in addition to T80 and P400 and evaluated for their saturated solubility, tabletop rheology, oil binding capacity, pH, spreadability, in vitro release, antibacterial activity, oscillatory rheology study, skin irritation, histological examination and ex- with in- vivo permeation study across rat abdominal skin. Results: The important results that distinguished organogels were the spreadability and in vitro release studies. The 4SO, 2OO, 2T80, and 10P400 organogels presented successful gelation and represented the lowest 12HSA concentration in each solvent that approached the current aim’s study by being more spreadable with higher CUR released. At the same time, the 2T80 and 10P400 gave zones of inhibition to 4 bacterial strains and good viscoelasticity by exhibiting large flow point values in the frequency sweep study compared with 4SO and 2OO. In vivo study affirmed the CUR permeation by studying the fluorescent images of 2T80 and 10P400, and the ex vivo permeation study for 10P400 proved the CUR permeation through rat’s skinOur results indicated the potential of 10P400 and 2T80 organogel to improve the topical therapeutic efficacy of CUR.

Quality by Design and Characterization of Nimodipine Novel Carriers for the Treatment of Hypertension: Assessment of the Pharmacokinetic Profile

Background: Nimodipine is a highly lipophilic anti-hypertensive drug having 13% oral bioavailability (log P 3.41). Nimodipine is a prominent calcium channel blocker that must be given intravenously for an extended period of time (1-2 weeks) in order to treat cerebral vasospasm. It might be possible to substitute a sustained-release biodegradable formulation for the ongoing intravenous infusion used in this traditional therapy. Objectives: The primary goal of this study was to formulate and evaluate the potentiality of ethosomes to deliver nimodipine, a potent water-insoluble anti-hypertensive drug, through the deeper layers of the skin. The greatest challenge for drug formulation is its poor oral bioavailability and solubility. Methods: Nimodipine-loaded ethosomal gel was developed for transdermal drug delivery to increase solubility and skin penetration and to promote oral bioavailability. Central composite design employing a thin-film hydration method was used to prepare and optimize ethosomes. A better dispersion medium for nimodipine's preparation in ethosomes was selected based on the effect. The design consisted of independent variables as lipid (X1), ethanol (X2), and sonication time (X3). Concentrations were manipulated to examine the effects on three responses, namely the %entrapment efficiency (Y1), vesicle size (Y2), and %cumulative drug release (Y3). Surface morphology and other in vitro tests were used to identify ethosomes containing nimodipine. The preparation of ethosomal gel formulations began with incorporating a single ethosomal formulation (F4) into various concentrations of gelling agents. These studies performed physicochemical characterization, compatibility testing, and in vitro drug release tests on ethosomal gels. In vivo studies involving hypertensive rats were conducted after skin permeation, and ex vivo studies were performed. In order to assess the drug's permeability and deposition, we employed the abdomen skin of rats. Results: The optimal process parameters resulted in ethosomes with 89.9 ± 0.19 percent entrapment efficiency, a vesicle size of 102.37 ± 5.84 nm, and a cumulative drug release of 98.3 ± 0.13%. pH and drug content measurements were consistent with the homogeneous ethosomal gels. Viscosity was found to increase with the spreadability. The ethosomal gel formulation (G2) met the regulatory standards regarding appearance, spreadability, viscosity, and in vitro release studies. Compared to pure nimodipine, ethosomal suspension (F4) and ethosomal gel (G2) formulations had higher ex vivo permeation, steady-state flux, and drug retention. Rats' mean arterial pressure (146.11 ± 0.84 mmHg) was significantly lower (p < 0.01) after after two hours of the experiment than it had been (p < 0.001) (98.88 ± 0.63 mmHg) after six hours. Conclusion: To summarize, ethosomal gels have been found to be lipid carriers that enhance skin permeation and extend the anti-hypertensive effect of nimodipine. Compared to plain gel, ex vivo drug permeation through rat abdominal skin in ethosomal gel was enhanced. Gel-based ethosomal transdermal drug delivery formulations of nimodipine can be used to achieve a faster rate and extend the duration of drug delivery by more than 24 hours.

Tween 80-Based Self-Assembled Mixed Micelles Boost Valsartan Transdermal Delivery.

Valsartan (Val) is an important antihypertensive medication with poor absorption and low oral bioavailability. These constraints are due to its poor solubility and dissolution rate. The purpose of this study was to optimize a mixed micelle system for the transdermal delivery of Val in order to improve its therapeutic performance by providing prolonged uniform drug levels while minimizing drug side effects. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including the surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with a low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta potential, and drug EE of the prepared micelles were all measured. The in vitro drug release profiles were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7 nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (p < 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm2/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. In summary, Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin-modifying enhancers.

Analysis of the permeable and retainable components of Cayratia japonica ointment through intact or broken skin after topical application by UPLC-Q-TOF-MS/MS combined with in vitro transdermal assay

Cayratia japonica ointment has been used for many years to promote wound healing after perianal abscess surgery. This study aimed to determine the skin-permeable and skin-retainable components of Cayratia japonica ointment after topical application to intact or broken skin via UPLC-Q-TOF-MS/MS analysis and in vitro transdermal assay. Moreover, a combination of semi-quantitative and molecular docking analyses was performed to identify the main active components of the Cayratia japonica ointment and the probable phases of the wound healing process that they act on. Modified vertical Franz diffusion cells and abdominal skin of rats were selected for the in vitro transdermal study. Mass spectrometry data were collected in both positive and negative ion modes. A total of 7 flavonoids (schaftoside, luteolin-7-O-glucuronide, luteolin-7-O-glucoside, apigenin-7-O-glucuronide, luteolin, apigenin, and chrysin) and 1 coumarin (esculetin), were found to permeate and/or retained by intact or broken skin. Among them, the flavonoids were more permeable through intact/broken skin and exhibited stronger binding affinities for targets related to the inflammatory and proliferative phases of wound healing. This study suggests that the flavonoids in Cayratia japonica ointment are most likely the main active components and are crucial at the inflammatory and proliferative phases of wound healing.

Dermal tissue penetration of in-plane silicon microneedles evaluated in skin-simulating hydrogel, rat skin and porcine skin

Recently, microneedle-based sensors have been introduced as novel strategy for in situ monitoring of biomarkers in the skin. Here, in-plane silicon microneedles with different dimensions and shapes are fabricated and their ability to penetrate skin is evaluated. Arrays with flat, triangular, hypodermic, lancet and pencil-shaped microneedles, with lengths of 500–1000 μm, widths of 200–400 μm and thickness of 180–500 μm are considered. Fracture force is higher than 20 N for all microneedle arrays (MNA) confirming a high mechanical stability of the microneedles. Penetration force in skin-simulating hydrogels, excised rat abdominal skin and porcine ear skin is at least five times lower than the fracture force for all MNA designs. The lowest force for skin penetration is required for triangular microneedles with a low width and thickness. Skin tissue staining and histological analysis of rat abdominal skin and porcine ear skin confirm successful penetration of the epidermis for all MNA designs. However, the penetration depth is between 100 and 300 μm, which is considerably lower than the microneedle length. Tissue damage estimated by visual analysis of the penetration hole is smallest for triangular microneedles. Penetration ability and tissue damage are compared to the skin prick test (SPT) needle applied in allergy testing.

Formulation and Evaluation of Double-layered (Matrix and Drug-in-adhesive) Transdermal Patches of Diclofenac Diethylamine: In vitro and ex vivo Permeation Studies

Abstract: Background: The objective of this current study was to fabricate and characterize the sustained release double layered transdermal patches of Diclofenac Diethylamine using hydrophobic acrylic polymer Eudragit RL 100 and hydrophilic polymer Polyvinyl pyrrolidone K-30 in combination as first layer of matrix type patch and pressure sensitive acrylic adhesive Duro Tak 387- 2510 as the second layer of drug-in-adhesive type patch to provide sustained anti-inflammatory effect. Materials and Methods: Solvent casting method was employed to prepare patch over the backing membrane. The double layered technique were attempted to create the desirable features of acrylic polymer and adhesive. The drug-polymers compatibility studies were examined by Infrared spectroscopy. A full-thickness excised abdominal rat skin sample was used to perform the permeation studies using Franz’s Diffusion Cell. Results: Drug-polymers compatibility studies revealed no evidence of interaction and the formulations showed satisfactory physicochemical-mechanical characteristics. It was found that release profiles were affected by the proportion of polymer and permeation enhancer used. The optimized formulation MF3 showed maximum in vitro and ex vivo percent cumulative drug permeated i.e. 87.28 ± 3.88% and 81.95 ± 2.64% respectively, with flux 12.96 ± 0.51 μg/ cm2/h and permeability coefficient 1.09 ± 0.45 cm/h, in 24 hr. Also, the permeation studies suggested that dimethyl sulphoxide exhibit more promising results as permeation enhancer. Conclusion: It was concluded that an ideal Diclofenac Diethylamine double layered transdermal patch would serve as the best carrier to provide sustained effect with desirable permeation enhancement characteristics. Keywords: Transdermal patches, Double layered technique, Hydrophobic acrylic polymer, Hydrophilic polymer, Permeation enhancer, Anti-inflammatory.

Topical delivery of mupirocin calcium nanostructured lipid carriers using a full-thickness excision wound healing model

Treatment of contaminated wounds represents a significant challenge in healthcare and there is a need to develop approaches maximising skin retention to maintain therapeutic concentrations of anti-infectives at the wound site. The objective of the present study was to develop and evaluate mupirocin calcium nanolipid emulgels to enhance wound healing performance and patient acceptability. Nanostructured lipid carriers (NLCs) of mupirocin calcium were prepared by the phase inversion temperature method using Precirol ATO 5 (Gattefosse, India) and oleic acid as lipids and Kolliphor RH 40 (BASF, India) as surfactant and further incorporated into a gel base for topical delivery. The particle size, polydispersity index and zeta potential of mupirocin NLCs were found to be 128.8±1.25nm, 0.283±0.003 and -24.2±0.56mV, respectively. In vitro release studies from developed emulgel showed sustained drug release over 24 hours. Ex vivo drug permeation studies through excised rat abdominal skin showed better skin permeation (1712.38±15. 57μg/cm2) from developed emulgel compared to marketed ointment (827.92±21.42μg/cm2) after 8 hours, which was in agreement with in vitro antibacterial activity. Studies on Wistar rats indicated the nonirritant potential of developed emulgels. Further, mupirocin emulgels showed improved efficacy in percent wound contraction of acute contaminated open wounds in Wistar rats using a full-thickness excision wound healing model. The emulgels of mupirocin calcium NLCs appear to be effective in the treatment of contaminated wounds due to increased skin deposition and sustained release, thereby enhancing the wound healing potential of existing molecules.

Evaluation of solid-lipid nanoparticles formulation of methotrexate for anti-psoriatic activity

Background & ObjectivesMethotrexate (MTX) is commonly used to manage psoriasis. The drug has erratic absorption characteristics and shows several complications. The present study uses different experimental models to evaluate the solid-lipid nanoparticles of MTX (SLN-MTX) for the anti-psoriatic effect. MethodsA prepared SLN-MTX formulation was used and its permeability studies were conducted on Wistar rat abdominal skin. The organ-level distribution of the drug in the formulation was tested in mice and the in-vitroanti-psoriatic activity was determined in CL-177; XB-2 keratinocytes cell lines. The efficacy of SLN-MTX formulation was compared with standard MTX and marketed MTX preparations. The results are analyzed statistically using the student’s t-test. ResultsThe data suggested that MTX from the formulation was slowly released and completely (80.36%) permeated through the skin. The flux and permeation data were found to be maximum for SLN-MTX compared to marketed and standard preparations. MTX in the formulation was found to be distributed more in the liver (67.5%) and kidney (2.34%). Further, SLN-MTXformulation showed dose-dependent inhibition on the growth of keratinocytes, and the cytotoxic concentration (CTC50) was found to be the least (518 mcg/ml). Interpretation & ConclusionThe findings suggested that MTX in solid-lipid nanoparticles could be a promising formulation for the management of psoriasis since the drug was slowly released, progressively inhibited the growth of keratinocytes, and distributed mostly in organs meant for elimination. More studies in this direction might establish the precise safety and efficacy of SLN-MTX formulation in psoriasis.

Investigation of the Effects of Cyclooxygenase I and Cyclooxygenase II Inhibitors on Angiogenesis in a Random-Pattern Rat Abdominal Skin Flap

Investigation of the Effects of Cyclooxygenase I and Cyclooxygenase II Inhibitors on Angiogenesis in a Random-Pattern Rat Abdominal Skin Flap

Preparation of liposomal hydrogel containing Calendula and application as a wound dressing.

Burn wound is one of the major medical and Hydrogels are one of the best wound dressings for burns. Herein, chitosan/Aloe vera hydrogel was prepared and cross-linked by genipin. The nano-liposomes of soy lecithin as a phospholipid containing calendula were added to the hydrogel. The surface morphology and functional groups were evaluated by SEM and FTIR methods, respectively. The average hydrodynamic diameter was calculated by the dynamic light scattering. Also, the nanoliposomes hydrogel containing calendula has a suitable swelling and vapor permeability. The encapsulation rate of calendula was 83 % which indicates a high load of calendula. In vivo release study of hydrogel containing calendula was achieved by the French diffusion cell. Finally, the cytotoxicity (MTT) test, the proliferation and viability of fibroblast cells (L929) were investigated and the results show no cytotoxicity of the hydrogel. for in vitro study, the passage of calendula-containing liposomes through the skin was investigated. Rat abdominal skin was used as a natural membrane. France diffusion cell was used as a two-compartment model to measure the amount of passage. The skin absorption of the calendula begins with a gentle slope and in 24 h approximately 90% of skin absorption has taken place.

Transferosomes versus transethosomes for the dermal delivery for minoxidil: Preparation and in vitro/ex vivo appraisal

Minoxidil is effective in the management of androgenic alopecia. However, a new drug delivery system is needed to maximize its efficacy and minimize side effects associated with its conventional formulation. Minoxidil was encapsulated into transferosomes and transethosomes and their particle size, polydispersity index, drug entrapment efficiency and in vitro drug release profiles were studied. Skin permeability and deposition were evaluated using rat abdominal skin. The particle size of the transethosomes (69.8 ± 1.4 to 167.4 ± 16.7 nm) was significantly smaller than that of the transferosomes (148.0 ± 0.3 to 364.2 ± 5.0 nm). Drug entrapment efficiency was significantly lower for the transethosomes (23.7 ± 3.2 to 47.2 ± 1.3%) compared to the transferosomes (77.0 ± 1.3 to 79.2 ± 0.1%). The drug release pattern was biphasic with a burst phase followed by a sustained release one. The transferosomes and transethosomes containing oleic acid had the best ability to sustain drug release. Transferosomes and transethosomes had respectively 2.84- and 3.36-fold enhancement in drug skin permeability compared with the drug hydroalcoholic solution. In addition, drug skin deposition was 28.5- and 18-fold higher in the stratum corneum and 3.6- and 6.5-fold higher in the epidermis/dermis for transferosomes and transethosomes, respectively compared with the drug hydroalcoholic solution. The transethosomes containing oleic acid had the highest permeability through the skin, highest deposition in deep skin layers and lowest deposition in stratum corneum. Transethosomes enhanced skin permeability and retention might improve minoxidil efficacy in the treatment of androgenic alopecia and reduce its side effects.

Initial research on the effect and mechanism of Tivozanib on pulsed dye laser induced angiogenesis

Pulsed dye laser (PDL) is the main treatment for port wine stain(PWS), but a considerable number of patients show low clearances. The reason for the poor efficacy is related to PDL-induced angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in PDL-induced angiogenesis and can activate the tyrosine kinase activity of VEGFreceptor (VEGFR) in endothelial cells. It triggers a full range of responses, and then participates in the regulation of angiogenesis. Tivozanib is an inhibitor of VEGFR tyrosine kinase activity, which can block the pro-angiogenic effect of VEGF and reduce vascular permeability. Different energy densities of PDL were used to irradiate the abdominal skin of rats. According to the general and pathological changes of the irradiated area, the energy density of 8 J/cm2 with smaller scab and stronger vascular effect was selected for follow-up experiments. Divided the rat abdomen skin into fourareas, irradiated three of them uniformly with an energy density of 8 J/cm2 , and applied different concentrations of Tivozanib coating agent to the laser irradiation area, and grouped them as follows: (1) vacant group, (2) control group, (3) 0.5% Tivozanib group, (4) 1% Tivozanib group. Camera and dermoscopy were used to observe skin changes. Hematoxylin-eosin staining, immunohistochemical staining, and blood vessels were counted to detect dermal vascular regeneration. Transcriptome sequencing and real-time polymerase chain reaction(PCR) were conducted to elucidate the mechanism and validate the reliability. The number of blood vessels in the 0.5% Tivozanib group and 1% Tivozanib group was significantly reduced on the 7, 10, and 14 days compared with the control group. The number of blood vessels in the 1% Tivozanib group was significantly reduced compared with the 0.5% Tivozanib group, indicating that Tivozanib successfully inhibited PDL-induced angiogenesis, and the inhibitory effect of 1% Tivozanib was more significant than that of 0.5% Tivozanib. Transcriptome sequencing results showed a total of 588 significantly differentially expressed genes, including 90 upregulated genes and 498 downregulated genes. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the significantly differentially expressed genes were mainly enriched in the metabolic pathways which were closely related to angiogenesis. Finally, real-time PCRwas used to verify the genes with higher expression differences, the top ranking and closely related to angiogenesis, namely, Cxcl1, Cxcl2, Cxcl3, Cxcl6, Ccl3, Csf3, IL1β, iNOS, Mmp9, Mmp13, Plau, Ets1, Spp1, Nr4a1. The results were consistent with the trend of transcriptome sequencing results, which proved the reliability of this study. This study explored the inhibitory effect of Tivozanib on PDL-induced angiogenesis, and provided a new idea for the treatment of clinical PWS. Transcriptome sequencing explored the mechanism and provided reliable clues for later in-depth research.

Perspective Impact of Gelling Agents on the Mechanistic Behavior for the Topical Delivery of Flufenamic Acid Nano-Ethosomal Dispersion

Objective: This work involves the preparation and in vitro characterization of a topical gel formulation that is capable of deep skin permeation, providing the anti-inflammatory effect for the optimum nano ethosomal dispersion formula. Methods: The optimum ethosomal dispersion was prepared (in our laboratory) by utilizing 3% flufenamic acid (FA), 30% ethanol, 1% phosphatidylcholine (PC), 10% propylene glycol, and 1% cholesterol by cold method and 20 minutes’ ultra-sonication. Four ethosomal gel formulas (G1-G4) were prepared by using carbopol 934 and carbopol 940 at 1% and 1.5% concentration at a 1:1 ratio as a gelling agent. These formulas were further subjected to in vitro characterization to assess their physical appearance, consistency, viscosity, spreadability, in vitro drug release, and ex-vivo skin permeation and deposition. Results: The results revealed that the formula (G1) demonstrated the best homogeneity, consistency, and spreadability as well as an initial release of 68.53% after 10 hours, that continued up to 89.36% after 24 hours, and a significantly higher drug release percentage at pH 7.4 than pH 5.5 with substantially higher ex vivo abdominal rat skin permeation (60.74%) and deposition percentages (36.87%%) in comparison to flufenamic acid plain gel prepared conventionally which demonstrated 23.73% and 14.96% skin permeation and deposition percentages after 24 hours. Conclusion: This work was successful in preparing a novel topical gel using ethosomal nanocarriers, promoting efficient topical skin delivery of the anti-inflammatory FA with a once-daily application, which improved patient compliance.

Fabrication of Ethosomes Containing Tocopherol Acetate to Enhance Transdermal Permeation: In Vitro and Ex Vivo Characterizations.

Background: Tocopherol acetate (TA) is known as a skin moisturizing and photoprotective agent. One major drawback with tocopherol and its derivatives remains its limited stability. Aim: To develop highly stable TA-containing ethosomal gel (TAEG) as an advanced dosage form. Methods: A cold method technique was used to produce the ethosomes. An in vitro evaluation of viscosity, conductivity, and pH stability was carried out for three months. An in vitro physical characterization of the nanoparticles (NPs) that included particle size (PS), zeta potential (ZP), transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy analysis was then performed. Organoleptic evaluation, thermostability at 8 °C, 25 °C, 40 °C and 40 °C ± 75% RH, pH, conductivity, viscosity, and spreadability measurements were also performed in vitro for three months. An ex vivo permeation study was performed in phosphate-buffered solution (1× PBS; pH 5.5 or pH 7.4) at 37 ± 0.2 °C by using rat abdominal skin and the Franz diffusion cell method. The data of three independent experiments were expressed as mean ± SD. A two-way ANOVA was applied to compare data on TAEG versus TA control gel (TACG). Results: PS of the ethosomes was in the range of 144–289 nm. A total of nine formulations were developed. Optimized TAEG formulation (TA-5) was selected based on the highest entrapment efficiency (EE) of 99.71%, while the stability, the PS, and the uniformity-based polydispersity index (PDI) were also among the best. TA-5 exhibited smooth spherical ethosomal NPs with PS of 200.6 nm, ZP value of −18.6 V, and PDI of 0.465. Stability data obtained for TA-5 in terms of rheology, conductivity, and pH presented no significant change (p > 0.05) during the entire study duration. Rheological studies indicated that TA-5 followed a non-Newtonian behavior of shear thinning system. The ex vivo drug permeation was 44.55 ± 0.01% in TA-5 and the drug retention in skin was 51.20%, which was significantly higher than TACG as observed after 24 h permeation study (p < 0.05). Conclusions: The newly developed TAEG formulation appears promising to enhance the effectivity of TA and its topical application.

Superiority of microemulsion-based hydrogel for non-steroidal anti-inflammatory drug transdermal delivery: a comparative safety and anti-nociceptive efficacy study

Non-steroidal anti-inflammatory drugs (NSAIDs) represent the foundation of pain management caused by inflammatory disorders. Nevertheless, their oral administration induces several side effects exemplified by gastric ulceration, thus, delivering NSAIDs via skin has become an attractive alternative. Herein, microemulsion-based hydrogel (MBH), proliposomal, and cubosomal gels were fabricated, loaded with diclofenac, and physicochemically characterized. The size, charge, surface morphology, and the state of diclofenac within the reconstituted gels were also addressed. The ex-vivo permeation study using Franz cells was performed via the rat abdominal skin. The formulations were assessed in-vivo on mice skin for their irritation effect and their anti-nociceptive efficacy through tail-flick test. Biosafety study of the optimal gel was also pointed out. The gels and their dispersion forms displayed accepted physicochemical properties. Diclofenac was released in a prolonged manner from the prepared gels. MBH revealed a significantly higher skin permeation and the foremost results regarding in-vivo assessment where no skin irritation or altered histopathological features were observed. MBH further induced a significant anti-nociceptive effect during the tail-flick test with a lower tendency to evoke systemic toxicity. Therefore, limonene-containing microemulsion hydrogel is a promising lipid-based vehicle to treat pain with superior safety and therapeutic efficacy.

DESIGNING OF NOVEL TOPICAL IN SITU POLYMERIC FILM-FORMING SOLUTION SPRAY FORMULATION OF ANTIFUNGAL AGENT: IN VITRO ACTIVITY AND IN VIVO CHARACTERIZATION

Objective: Voriconazole (VCZ) is a broad-spectrum antifungal medication that works by inhibiting fungal Cytochrome P450, preventing fungi growth. The current study aims at developing and characterizing an antifungal in situ film-forming polymeric solution spray containing VCZ for use in topical drug delivery systems. Methods: Optimized VCZ in situ polymeric film formulation was evaluated for Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffractometry (XRD), Scanning electron microscope (SEM), in vitro and in vivo, ex-vivo investigation using abdominal rat skin and stability studies. The in vivo antifungal activity of the advanced in situ film was examined in albino Wistar rats. Results: The optimized batch contained 22% Eudragit RS 100 (ERS) and 4% Sorbitol. Based on FTIR, XRD, SEM, and rheological studies. Formulation ingredients of VCZ loaded topical in situ polymeric film spray were observed to be compatible and showed no evidence of precipitation, deformation, or discoloration. Diffusion test (in vitro %), and ex-vivo drug diffusion % obtained 99.22%, and 97.45% respectively. The maximum inhibition zone was measured at 13±0.07 mm. The Wistar rat was employed as an animal model for skin irritation and antifungal studies. A study of short-term stability observed no significant modifications in the physical properties. Conclusion: The findings of the optimized VCZ topical in situ polymeric film spray formulation were satisfactory, demonstrating comparable improvement in superficial antifungal treatment.

Formulation and Development of Adapalene Topical Nanohydrogel Using Different Surfactants and Cosurfactants for Antiacne Activity: In Vitro and Ex Vivo Evaluation

A formulation of an adapalene nanohydrogel (ADP‐NH) using different surfactants and cosurfactants for topical application was developed and characterized. The best formulation was obtained with nanohydrogel (NH) containing Tween‐80‐ (NH‐Tween‐80‐) incorporated carbopol‐940 and ethanol, 0.67% and 3.00% w/w, respectively. The optimized formulations of NH‐Tween‐80, nanohydrogel containing sodium lauryl sulphate (NH‐SLS), and nanohydrogel containing glycerol (NH‐glycerol) were separately evaluated to examine their in vitro and ex vivo permeability characteristics and compared with 0.3% dimethyl sulfoxide (control) solution. The polydispersity index of NH‐Tween‐80, NH‐SLS, and NH‐glycerol were found to be 0.264 ± 0.312, 0.382 ± 0.0045, and 0.310 ± 0.412, respectively. All NH formulations showed pH within human skin pH ranges throughout the stability period. The NH‐Tween‐80 revealed 191.22 μg/mL of ADP permeation through Strat‐M® membrane which was statistically significant (p &lt; 0.05) compared to NH‐SLS, NH‐glycerol, and control solution. At 24 h, NH‐Tween‐80 demonstrated 305.11 μg/mL of ADP permeation in Wistar rat abdominal skin which was 1.99‐, 1.56‐, and 4.89‐fold higher in comparison with NH‐SLS, NH‐glycerol, and control solution, respectively. Moreover, the ex vivo permeability of NH‐Tween‐80 was also compared with conventional gel (market sample) which was 3.38‐fold greater at 24 h. During the 6th month of accelerated stability analysis, the NH‐Tween‐80, NH‐SLS, and NH‐glycerol demonstrated 99.25% ± 0.15, 91.23% ± 0.41, and 96.08% ± 0.20 drug content, respectively. There were no noticeable physical changes observed up to 6 months for NH‐Tween‐80, while color change was observed in the 1st month and 3rd month of accelerated stability samples of NH‐SLS and NH‐glycerol, respectively. In this study, only NH‐Tween‐80 was considered both physically and chemically stable formulation. Therefore, it was concluded that the topical application of ADP‐NH containing Tween‐80 could be a very promising alternative for the treatment of acne vulgaris.

Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612).